The close anatomical relationship between the septal nuclei and the hippocampus within the limbic system is well known. Much recent research, at the cellular level, has been concerned with the physiology and pharmacology of neurons within the hippocampus, but little comparable data is available about neurons in the septal nuclei. We have developed an in vitro brain slice preparation to record intracellularly from individual rat dorsolateral and medial septal neurons. Our goal is to characterize individual septal neurons on an electrophysiological, pharmacological and anatomical bases so that we can determine which specific neurons in these nuclei serve a "pacemaker" function and how these neurons generate an electrical activity termed theta rhythm. Theta rhythm can be recorded from various parts of the limbic system, but its focus of origin is currently thought to reside either in the septum or the hippocampus. We will proceed on the hypothesis that theta rhythm is generated in the septum and determine how this rhythm is affected by endogenously released neurotransmitters such as: norepinephrine, dopamine, serotonin, acetylcholine or excitatory and inhibitory amino acids. We will compare responses induced by exogenous, iontophoretic application of these same substances on septal neurons. Finally, we will examine how benzodiazepines, the most often prescribed behaviorally active drugs, affect both spontaneous and evoked electrical activity. We believe information obtained from this proposal will have broad basic and clinical science applications, since modification of septal neuron activity has been implicated in both normal and abnormal cognitive processes such as learning and memory, and in normal and abnormal expressions of our emotions. Specific mental disorders that may benefit from the results of this proposal include: schizophrenia, depression, mania, epilepsy, senile dementia, and Alzheimer's Disease.